Stroke-prone spontaneously hypertensive rats (SHRSP) are at increased risk of cerebral infarction. In SHRSP, but not in the normotensive reference strain (WKY), a large infarct occurs after occlusion of a major cerebral artery. The infarct location within the territory normally supplied by the occluded vessel suggests inadequate collateral circulation. We hypothesize that deficient vasodilation of the anastomosis (midzone collateral) predisposes SHRSP to infarction. Long- term objectives are to characterize the pathophysiology of the cerebral collateral circulation in SHRSP and to investigate mechanisms to improve this flow. The specific aims are to 1) assess pial artery blood pressure and vascular conductance to determine if the deficient vasodilation is located primarily within cortex or in small (less than 75mu/m, i.d.) pial surface anastomoses, 2) identify possible cellular regulatory mechanisms (nitric oxide synthase, cholinergic, serotonergic) responsible for inadequate vasodilation or reduced collateral blood flow through small anastomoses, 3) determine the mechanism by which chronic unilateral common carotid occlusion protects SHRSP against a large ipsilateral infarct after middle cerebral artery occlusion, 4) identify the abnormality in a large (greater than 150 mu/m, id.d) anastomosis and characterize the effect of increased hemodynamic load (flow conditioning) on the abnormality and development of the anastomosis, and 5) determine if the dilator deficiency in SHRSP is also present in a selectively bred normotensive cognitive strain having the stroke characteristic and in the hypertensive protected congenic strain. Accomplishments of the objectives is expected to provide better insight needed for making interventions to alter vascular pathophysiologic mechanisms of hypertension that predispose to stroke.